Sensitive UHPLC-MS/SRM method for quantifying olanzapine metabolites and degradation products from sera

Abstract

In recent years, the use of antipsychotics like olanzapine has increased leading to potentially serious adverse metabolic effects. A sensitive method to quantify olanzapine and its metabolites is therefore highly needed. A stable isotope dilution ultrahigh performance liquid chromatography-mass spectrometry/selected reaction monitoring based quantitative assay has been developed for the simultaneous estimation of olanzapine and its metabolites. This method includes the parent drug olanzapine, its metabolites (desmethyl olanzapine and olanzapine-N-oxide) and degradation derived piperazinium chloride, lactam and cyclic amine impurities. All analytes were well resolved and showed a linear relationship across a large dynamic range (0.017–1.25 ng mL⁻¹) for all olanzapine metabolites except the lactam, in which the linear relationship was demonstrated at concentrations five times higher (0.085–6.25 ng mL⁻¹). All analytes had regression coefficients higher than 0.998, accuracies between 92–113% and low coefficients of variation (0.94 to 9.3%). The recovery for all of the analytes from the sera matrix was 80 to 115%. This validated method is suitable for quantifying olanzapine and its metabolites from small volumes of sera samples with great sensitivity.